Vistaril - Drug Monograph

Introduction

Vistaril (hydroxyzine) is a first-generation antihistamine with anxiolytic, antiemetic, antispasmodic, and sedative properties. Originally developed in the 1950s, it remains clinically relevant due to its multifaceted pharmacological profile and favorable safety record compared to benzodiazepines. Hydroxyzine is available as hydroxyzine pamoate (Vistaril) and hydroxyzine hydrochloride, with both formulations offering similar therapeutic effects.

Mechanism of Action

Hydroxyzine primarily acts as a potent antagonist at histamine H₁ receptors, producing antihistaminic effects. Its anxiolytic properties result from suppression of activity in key subcortical regions of the central nervous system, particularly the hypothalamus. Unlike benzodiazepines, hydroxyzine does not act on GABA receptors, making it non-addictive and avoiding the risk of physical dependence associated with scheduled anxiolytics. Additional anticholinergic and antiserotonergic activity contributes to its antiemetic and antipruritic effects.

Indications

FDA-approved indications:

• Management of anxiety disorders and tension
• Preoperative and postoperative adjunctive medication for sedation
• Pruritus associated with allergic conditions
• Antiemetic therapy for post-operative nausea

Off-label uses:

• Insomnia (particularly anxiety-related)
• Adjunct therapy for opioid withdrawal symptoms
• Treatment of acute urticaria
• Psychogenic itching disorders

Dosage and Administration

• Anxiety: 50-100 mg PO QID or 50-100 mg IM Q4-6H (max 600 mg/day)
• Pruritus: 25 mg PO TID-QID
• Preoperative sedation: 50-100 mg IM
• Postoperative nausea: 25-100 mg IM

Initiate with lower doses (25 mg PO BID-TID) due to increased sensitivity to anticholinergic effects

• Under 6 years: 50 mg/day PO in divided doses
• Over 6 years: 50-100 mg/day PO in divided doses

• IM administration preferred over IV due to risk of thrombosis and hemolysis
• Oral administration with food may reduce GI upset
• Shake oral suspension well before use

Pharmacokinetics

Contraindications

• Hypersensitivity to hydroxyzine or any component of the formulation
• Early pregnancy (first trimester)
• Patients with prolonged QT interval or significant risk factors for torsades de pointes
• Acute narrow-angle glaucoma
• Benign prostatic hyperplasia with urinary retention

Warnings and Precautions

• CNS depression: May impair mental and physical abilities; caution when operating machinery
• QT prolongation: Monitor in patients with cardiac conditions or taking other QT-prolonging drugs
• Anticholinergic effects: Use with caution in elderly patients due to risk of confusion, dry mouth, constipation, and urinary retention
• Seizure disorders: May lower seizure threshold
• Hepatic impairment: Requires dose adjustment due to extensive hepatic metabolism
• Renal impairment: Use with caution; monitor for increased adverse effects

Drug Interactions

• CNS depressants (alcohol, opioids, benzodiazepines): Additive sedation
• Anticholinergic agents (tricyclic antidepressants, antipsychotics): Enhanced anticholinergic effects
• QT-prolonging drugs (antiarrhythmics, macrolides, fluoroquinolones): Increased risk of torsades de pointes
• Monoamine oxidase inhibitors: May potentiate anticholinergic effects

• Cholinergic agents (bethanechol): Reduced effectiveness
• CYP2D6 inhibitors: May increase hydroxyzine concentrations

Adverse Effects

• Somnolence (40-50%)
• Dry mouth (20-30%)
• Dizziness (5-10%)
• Headache (5-8%)
• Fatigue (5-7%)

• Constipation
• Blurred vision
• Urinary retention
• Tachycardia
• Hypotension
• Tremor
• Skin reactions

• QT prolongation and torsades de pointes
• Seizures
• Severe hypersensitivity reactions
• Blood dyscrasias (leukopenia, thrombocytopenia)

Monitoring Parameters

• Comprehensive medical history with focus on cardiac, hepatic, and renal function
• ECG if cardiac risk factors present
• Pregnancy test in women of childbearing potential

• Mental status and sedation level
• Signs of anticholinergic toxicity
• Renal and hepatic function (periodically)
• ECG monitoring if high doses or concomitant QT-prolonging drugs
• Therapeutic response and adverse effects

• Elderly: Frequent assessment of cognitive function
• Hepatic impairment: Monitor for increased sedation
• Pediatric: Growth monitoring with long-term use

Patient Education

• Take exactly as prescribed; do not increase dose without consultation
• Avoid alcohol and other CNS depressants during treatment
• May cause drowsiness - avoid driving or operating dangerous machinery until effects are known
• Rise slowly from sitting/lying position to prevent dizziness
• Use sugar-free candy or gum to relieve dry mouth
• Report any palpitations, fainting, or difficulty urinating immediately
• Do not stop abruptly if used long-term; taper under medical supervision
• Inform all healthcare providers of hydroxyzine use before procedures

• Store at room temperature (15-30°C)
• Keep away from moisture and light
• Oral suspension: shake well before use
• Keep out of reach of children

References

1. FDA Prescribing Information: Vistaril (hydroxyzine pamoate) 2. Katzung BG, et al. Basic & Clinical Pharmacology. 14th ed. McGraw-Hill; 2018 3. Brunton LL, et al. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill; 2017 4. PDR Drug Information for Hydroxyzine. Medical Economics; 2023 5. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023 6. Lexicomp Online [database]. Hudson, OH: Wolters Kluwer Clinical Drug Information; 2023 7. Joint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press; 2023